The proposed preclinical studies would address several issues that concern the vaccination program in human cocaine addicts in an effort to both evaluate the proposed clinical designs and to provide direction for future strategies. In accordance with these goals, the Specific Aims of Project 2 are as follows: 1. To determine if anti-cocaine antibodies block both the discriminative stimulus and reinforcing stimulus effects of cocaine and if the outcome of each procedure in rats can predict the clinical efficacy of the vaccine. 2. To determine the behavioral specificity of the decreases in self-administration responding engendered by anti-cocaine antibodies and other co-medications by examining their effects on responding maintained by a non-drug reinforcer. 3. To determine if cocaine use during the immunization period will alter the efficacy of the vaccine. 4. To determine the synergistic effects of the vaccine with other co-medications for reducing cocaine self-administration during and after the immunization period. By way of background and significance, the proposal indicates that an important component of medications development for cocaine addiction treatment is the development of cocaine antagonists. Along these lines, the feasibility of an antibody approach for blocking the effects of cocaine has been demonstrated to some extent. Further, passive administration experiments conducted in the PI?s laboratory suggested that a blockade of the reinforcing effects of self-administered cocaine may be conferred by anti-cocaine antibodies. Since addiction to cocaine is thought to be related to both its reinforcing and discriminative stimulus effects, the proposal presents plans to use intravenous self-administration and drug discrimination procedures to extend these initial findings. Since drug self-administration behavior in animals positively correlates with abuse of that drug by human subjects and drug effects in drug discrimination tests in animals positively correlate with subjective effects in human subjects, it is hypothesized that anti-cocaine antibodies should block both of these properties without producing any non-specific behavioral effects to be maximally effective in treating people addicted to cocaine.